Hydrochloric Acid → 3-[4-[(2'-Methyl-6'-propylbiphenyl-3-yl)methoxy]phenyl]propanoic acid

HRID 2422276Notes

Reaction equation

HRID 2422276 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([O:12]C)=[O:11])=[CH:4][CH:3]=1.[CH3:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][CH2:22][CH3:23])[C:16]=1[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30]O)[CH:25]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.Cl>O1CCCC1.CO.[OH-].[Na+].C(OCC)C>[CH3:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][CH2:22][CH3:23])[C:16]=1[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][O:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[CH:6][CH:7]=2)[CH:25]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 79706Benzenepropanoic acid, 4-hydroxy-, methyl esterHCID 23083171(2'-Methyl-6'-propylbiphenyl-3-yl)methanol

Product 1

HCID 575420103-[4-[(2'-Methyl-6'-propylbiphenyl-3-yl)methoxy]phenyl]propanoic acidYield 59.4%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of methyl 3-(4-hydroxyphenyl)propanoate (0.21 g, 1.14 mmol), (2′-methyl-6′-propylbiphenyl-3-yl)methanol (0.25 g, 1.04 mmol) and tributylphosphine (0.39 mL, 1.56 mmol) in tetrahydrofuran (6 mL) was added 1,1′-(azodicarbonyl)dipiperidine (0.39 g, 1.56 mmol) with stirring at 0° C., and the mixture was stirred at room temperature for 16 hrs. Diethyl ether was added to the reaction mixture, the insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-hexane/ethyl acetate=4/1) to give as a colorless oil. This product was then dissolved in a mixed solution of methanol (4.0 mL) and tetrahydrofuran (6.0 mL), 1N aqueous sodium hydroxide solution (2.28 mL) was added at room temperature with stirring, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was adjusted to pH 3 with 1N hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried (anhydrous magnesium sulfate), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1-1/2) to give the title compound (0.24 g, yield 59%) as colorless crystals. MS (APCI−): 387 (M−H).

Workup

  1. stirringthe mixture was stirred at room temperature for 16 hrs
  2. filtrationthe insoluble material was filtered off
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane-hexane/ethyl acetate=4/1)
  5. customto give as a colorless oil
  6. additionwas added at room temperature
  7. stirringwith stirring
  8. stirringthe mixture was stirred at room temperature for 1 hr
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe organic layer was washed with water and saturated brine
  11. dry with materialdried (anhydrous magnesium sulfate)
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1-1/2)

Sources & evidence

ORD record
ord-384ee33764aa42c79c06ee022ad824f2
Source dataset
uspto-grants-2011_06
Patent number
US07960369B2

Reaction notes

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